DESCRIPTION This application is based on preliminary findings that pial arterioles in newborn pigs constrict and cerebral blood flow and metabolism are decreased after fluid percussion injury in brain. The overall hypothesis is that opioids contribute to this reduction in cerebral blood flow and possibly to secondary cerebral ischemia in this model. To examine this hypothesis, three specific aims are planned using newborn and juvenile piglets: 1) to characterize the relationship between local periarachnoid concentrations of opioids, cerebral hemodynamics, and oxygenation following fluid injury, 2) to determine the functional significance of the relationship between brain opioids, brain oxygenation and the cerebral circulation following fluid injury, and 3) to investigate the mechanisms by which endogenous opioids affect cerebral vascular responses subsequent to fluid percussion injury. Vascular responses in these experiments will be measured using radioactive microspheres and a closed cranial window preparation. Local levels of opioids and prostanoids in cerebrospinal fluid will be measured using radioimmunoassay. An index of cerebral oxygenation will be obtained using near infrared spectroscopy. These studies will explore mechanisms involved in regulation of cerebral blood flow in a brain injury model in newborn pigs and should provide new information in an area where few data are available. The investigators suggest that experimental findings may have clinical relevance for mechanisms of head injury.